title: Novel role of the renin-angiotensin system in preeclampsia superimposed on chronic hypertension and the effects of exercise in a mouse model.
abstract: Gestational hypertensive disorders, such as preeclampsia, affect 6% to 8% of all pregnancies in North America, and they are the leading cause of maternal mortality in industrialized countries, accounting for 16% of deaths. Women with hypertension have an increased risk (15% to 25%) of developing preeclampsia. Our aim was to investigate the mechanisms implicated in preeclampsia superimposed on chronic hypertension and in the protective effects of exercise in a mouse model. Female mice overexpressing human angiotensinogen and human renin were used as a model of preeclampsia superimposed on chronic hypertension. In the trained group, mothers were placed in cages with access to a wheel before mating, and they remained within these throughout gestation. Blood pressure was measured by telemetry. We found that angiotensin II type I receptor was increased, whereas the Mas receptor was decreased in the placenta and the aorta of pregnant sedentary transgenic mice. This would produce a decrease in angiotensin-(1-7) effects in favor of angiotensin II. Supporting the functional contribution of this modulation, we found that the prevention of most pathological features in trained transgenic mice was associated with a normalization of placental angiotensin II type 1 and Mas receptors and an increase in aortic Mas receptor. We also found reduced circulating and placental soluble Fms-like tyrosine kinase-1 in trained transgenic mice compared with sedentary mice. This study demonstrates that modulation of the renin-angiotensin system is a key mechanism in the development of preeclampsia superimposed on chronic hypertension, which can be altered by exercise training to prevent disease features in an animal model.
authors.affiliation: CRCHUM - Technopôle Angus, 2901 Rachel St E, Suite 310, Montreal, Quebec H1W 4A4, Canada. julie.lavoie.3@umontreal.ca.
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Genest
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Falcao
authors.forename: Catherine
authors.initials: C
authors.lastname: Michel
authors.forename: Sonia
authors.initials: S
authors.lastname: Kajla
authors.forename: Mark F
authors.initials: MF
authors.lastname: Germano
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Lacasse
authors.forename: Cathy
authors.initials: C
authors.lastname: Vaillancourt
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gutkowska
authors.forename: Julie L
authors.initials: JL
authors.lastname: Lavoie
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology; D062186:Arterial Pressure / Q000502:physiology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010920:Placenta / Q000378:metabolism / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D015854:Up-Regulation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: angiogenic factor; angiotensin-(1–7); exercise; preeclampsia; renin–angiotensin system